caa a22 4500 477072445 CHVBK 20180405111430.0 cr unu---uuuuu 170330e19960901xx s 000 0 eng 10.1007/BF00051106 doi (NATIONALLICENCE)springer-10.1007/BF00051106 Calcium-channel blockers inhibit human low-density lipoprotein oxidation by oxygen radicals [Elektronische Daten] [Claudio Napoli, Massimo Chiariello, Giuseppe Palumbo, Giuseppe Ambrosio] Summary: Previous studies have shown that calcium channel blockers may reduce the development of experimental athero-sclerosis, and that nifedipine may slow the progression of coronary atherosclerosis in humans. The mechanisms responsible for this antiatherogenic effect are still unclear. It has been recently proposed that oxygen free radicals can induce the oxidation of human low-density lipoproteins (LDL) and that oxidized LDL may be an atherogenic stimulus. Previous studies in other systems have shown that calcium channel blockers may effectively inhibit oxygen radical-induced lipid peroxidation in vitro. Thus, the aim of the present study was to investigate whether calcium channel blockers may also reduce LDL modifications induced by oxygen radicals. Isolated human LDL were exposed to oxygen radicals generated by CuSO4 (10 μM for 18 hours) after a 30 minute preincubation with different concentrations (1-100 μM) of nifedipine, diltiazem, and verapamil. Lipid peroxidation was measured from malonyldihaldehyde (MDA) production. Oxygen radical-induced damage on apolipoprotein-B100 was evaluated by acrylamide and agarose gel electrophoresis. Calcium channel blockers dose-dependently prevented oxidation of both the lipid and protein components of LDL. MDA formation was reduced in LDL pre-incubated with calcium antagonists before exposure to oxygen radicals (% MDA inhibition was 89.8±6.9 with 30 μM nifedipine, 68.6±4.9 with 30 μM verapamil, and 65.6±7.1 with 30 μM diltiazem; p< 0.01 vs. controls). Similarly, apolipoprotein-B100 integrity was preserved against oxygen radical attack in the presence of calcium antagonists. Thus, calcium channel blockers reduce the oxidation of human LDL in vitro. These data suggest that reduced formation of atherogenic oxidized LDL may be an additional mechanism for the antiatherosclerotic effects of calcium channel blockers in vivo. Kluwer Academic Publishers, 1996 low density lipoprotein nationallicence calcium channel-blockers nationallicence oxygen radicals nationallicence atherosclerosis nationallicence peroxidation nationallicence Napoli Claudio Division of Cardiology "Federico II” School of Medicine, University of Naples, Naples, Italy aut Chiariello Massimo Division of Cardiology "Federico II” School of Medicine, University of Naples, Naples, Italy aut Palumbo Giuseppe Department of Cellular and Molecular Pathology, "Federico II” School of Medicine, University of Naples, Naples, Italy aut Ambrosio Giuseppe Division of Cardiology "Federico II” School of Medicine, University of Naples, Naples, Italy aut Cardiovascular Drugs and Therapy Kluwer Academic Publishers 10/4(1996-09-01), 417-424 0920-3206 10:4<417 1996 10 10557 https://doi.org/10.1007/BF00051106 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/BF00051106 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Napoli Claudio Division of Cardiology "Federico II” School of Medicine, University of Naples, Naples, Italy aut NATIONALLICENCE 700 1- Chiariello Massimo Division of Cardiology "Federico II” School of Medicine, University of Naples, Naples, Italy aut NATIONALLICENCE 700 1- Palumbo Giuseppe Department of Cellular and Molecular Pathology, "Federico II” School of Medicine, University of Naples, Naples, Italy aut NATIONALLICENCE 700 1- Ambrosio Giuseppe Division of Cardiology "Federico II” School of Medicine, University of Naples, Naples, Italy aut NATIONALLICENCE 773 0- Cardiovascular Drugs and Therapy Kluwer Academic Publishers 10/4(1996-09-01), 417-424 0920-3206 10:4<417 1996 10 10557 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer